1. Catherine Moore 1 Jörg Hoffmann 2, Maurizio Brotto 3 and Rachel Jones 1 1. Wales Specialist virology centre, Public Health Wales Microbiology Cardiff 2.Mid and West Wales Health Protection Team, Swansea 3. Department of pathology, Singleton hospital, Swansea Catherine Moore 1 Jörg Hoffmann 2, Maurizio Brotto 3 and Rachel Jones 1 1. Wales Specialist virology centre, Public Health Wales Microbiology Cardiff 2.Mid and West Wales Health Protection Team, Swansea 3. Department of pathology, Singleton hospital, Swansea Background During the large measles outbreak that occurred in South Wales in 2013 severe complications were rarely reported. However, on the 19 th April 2013 the Mid and West Health Protection Team of Public Health Wales received a report of the sudden death in the community of a 24 year old man with a 6 year history of alcohol dependency (on treatment) and rash illness with an onset 4 days prior to death. He had no prior history of immunisation with MMR. With the increased media interest, it was important to quickly establish whether measles was a factor in the death. To facilitate this, a throat swab and EDTA blood was collected the same day from the body and sent to the Public Health Wales Laboratory in Cardiff for rapid measles PCR testing as previously described 1. Both samples were positive for measles virus RNA, thus confirming that the case had died with a measles virus infection. The throat swab result was confirmed by the UK measles virus reference laboratory in London. At this point, measles could not be confirmed as cause of death, and so a coroners autopsy was requested to be undertaken to determine cause and was performed one week post death. Sampling during autopsy As molecular testing was to be undertaken for specific measles PCR, the pathologist performing the autopsy was instructed to take sterile swabs and return them dry to the laboratory for testing. Swabs were taken from external and internal sites including from the brain, kidney and throughout the respiratory tract (table 1). Additional bacteriology and tissue samples (lung and brain) for histological examination were collected following local protocols and guidelines. Urine and blood were sent for toxicology. Results The initial observations were of a young man with low BMI, the body surface was covered in a red-brown rash with areas of desquamation on the face and ears. Koplik’s spots were observed on the oral mucosa extending into the larynx. The conjunctiva showed focal erosions with foci of pus. The surface of the lungs showed diffuse punctiform haemorrhage and within the left and right lung lobes areas of oedema, consolidation and pus were observed. The measles virus PCR was performed on all samples simultaneously. Despite the delay from death until autopsy, all samples collected were positive for measles RNA with increasing amounts detected the further down the respiratory tract the samples were collected (table 1). Toxicology was negative and nothing abnormal was observed in the brain histology. The lung histology showed multinucleated giant cells, typical of that seen in Hecht’s pneumonia (picture from actual case not available, example shown in figure 1). Site of swabMeasles virus Ct valueRNaseP Ct Value Meninges35.226.1 Cerebellum35.027.9 Deep brain33.027.4 Kidney29.828.3 Blood29.025.0 Eye23.828.4 Ear22.325.4 Mouth22.129.0 Larynx21.929.4 Bronchi19.528.6 Lung18.828.7 Cut surface of lung17.829.4 Figure 1. Classical measles giant cell formation in lung tissue (Hecht’s pneumonia). Adapted from Schaechler’s mechanisms of of Microbial Disease. 4 th Ed. Engleberg, DiRita and Dermody: Lippencott, Williams and Wilkins; 2007; Fig.34-3 Table 1. Threshold crossing values of the real-time PCR for measles virus and internal control RNaseP by swab site. Conclusions Complications associated with measles infections occur most frequently in children under 5 years, in adults over 20 years, in the immunocompromised and in cases of malnutrition. The most common cause of death is due to pneumonia. In the fatal case described, although not immunocompromised, a history of alcohol dependency and low BMI together with age at onset, increased the risk for complications. The virology results demonstrated the systemic nature of measles virus infection, with measles RNA detected in all swabbed sites. The high levels of measles RNA detected in the lung samples supported the coroner’s conclusion that cause of death was due to measles virus pneumonia. Once the number of notified cases reached over 1000 in the outbreak area, it was almost inevitable that there would be a fatality. The outbreak itself occurred in the generation directly affected by the anti-MMR vaccination campaigns of the early 1990’s. It is a sad fact that without the negative impact of the campaign, that immunisation rates would have reached 95% in this age group and that both the outbreak and consequently this fatal case would have been avoided. 1.C. Moore et al. (2015) Self-collected buccal swabs and rapid, real-time PCR during a large measles outbreak in Wales: Evidence for the protective effect of prior MMR immunisation; Journal Clin Virology, Vol 67 pages 1-7 Acknowledgements. The staff of Public Health Wales and the Virus Reference Laboratory in London. Special acknowledgement to the family of the case presented.